Magnetic Sorter Channels for Stem Cells

描述（由申请人提供）：SHOT建议研究导致从人脐带血，骨髓和外周血分离产物细胞中磁分离造血干细胞技术的商业化。骨髓移植（BMT）是治疗某些白血病和其他血液病的一种有效方法。同种异体BMT的高治愈潜力受到组织相容性匹配供体的限制，以尽量减少移植物抗宿主病的可能性。分离干细胞的能力为设计最合适的移植物开辟了新的临床途径。在第一阶段的研究中，SHOT的合作者在克利夫兰诊所基金会建立了四极磁流分选器（QMS），相对于大多数其他方法，它具有更高的产量和容量，满足了血液干细胞选择的大部分要求，SHOT展示了无菌一次性磁流通道和QMS系统的原型制造。因此，II期研究需要设计一个包装，包括一个自动化的QMS设备和一次性通道，具有足够的精度、可重复性和容量，最终符合临床环境中人类造血干细胞分离的要求。SHOT将(1)进行研究，将QMS系统可处理的样本量从140毫升增加到500毫升；(2)研究免疫磁性标记技术，提高标记细胞的磁性迁移率，从而提高样品处理速度；(3)根据现行良好生产规范（cGMP）设计指南，完善质量管理体系设计，吸取经验教训，使体系更快、更通用、更方便使用；(4)在全国知名的癌症和细胞治疗实验室完成测试项目。拟议的II期最终项目是两个上市前制造的QMS系统原型和一套能够支持beta测试程序并准备好进行cGMP验证过程的精细分离通道。SHOT的QMS系统的目标是能够分选1000万个细胞/秒，总通量为8ml /min或更高，回收率和纯度为60%或更高。III期活动将包括在研究市场销售的QMS系统和分离渠道的生产，以及在临床环境中根据cGMP销售QMS系统和分离渠道的FDA合规的直接努力。

DESCRIPTION (provided by applicant): SHOT proposes research leading to the commercialization of technology for magnetic isolation of hematopoietic stem cells from human umbilical cord blood, bone marrow and peripheral apheresis product cells. Bone marrow transplantation (BMT) is an established therapy for certain leukemias and other hematologic diseases. The high cure potential of allogeneic BMT is limited by the need for matched histocompatible donors to minimize the possibility of graft-versus-host disease. The ability to isolate stem cells opens a new clinical approach for engineering a most suitable graft. In Phase I research SHOT'S collaborators at The Cleveland Clinic Foundation established that the Quadrupole Magnetic (flow) Sorter (QMS) fulfills most of the requirements for hematologic stem cell selection with its much higher yield and capacity relative to most other methods, and SHOT demonstrated the manufacture of prototype sterile disposable magnetic flow channels and a QMS system. Phase II research thus calls for the design of a package, consisting of an automated QMS facility and disposable channels with sufficient precision, reproducibility and capacity to qualify ultimately for the isolation of human hematopoietic stem cells in the clinical setting. SHOT will (1) perform research to increase the sample size that the QMS system can process from 140 ml to 500 ml; (2) investigate imumunomagnetic labeling technologies to increase the magnetic mobility of the labeled cells, thus increasing sample processing speed; (3) refine the QMS system design in accordance with Current Good Manufacturing Practices (cGMP) design guidelines to incorporate lessons learned, making the system faster, more versatile and more user-friendly; and (4) complete a betatesting program in nationally-known cancer and cell therapy laboratories. The proposed Phase II end items are two pre-market manufactured QMS system prototypes and a set of refined separation channels capable of supporting the beta testing program and ready for the cGMP verification process. SHOT'S goal for the QMS system is the capability of sorting 10 million cells/sec at a total throughput of 8 ml/min or greater with a recovery and purity of 60% or greater. Phase III activities will include manufacture of the QMS systems and separation channels for sale in the research market, as well as a directed effort towards FDA compliance for sales of the QMS systems and separation channels under cGMP in the clinical setting.